HIV, the causative agent of AIDS, has been infrequently recovered from salivary secretions. Preliminary reports support the contention that human saliva contains inhibitory activity directed against HIV> The specific aims of this project are to (1) verify and amplify the anti-HIV effects of saliva, (2) fractionate the salivas (parotid, submandibular/sublingual and/or labial) with the activity to isolate the component(s), (3) identify and characterize the biologic and molecular nature of the substance(s), and (4) determine the mechanism of anti-HIV action of the active component(s). Human whole and individual gland salivary secretions will be obtained from normal human subjects and tested for anti-HIV activity utilizing a sensitive, standardized, and reproducible human host-cell in vitro screening assay (MT-2 syncytium-formation TCID50 assay). Those glandular secretions showing inhibitory activity toward HIV infectivity will be fractionated and individual fractions possessing the inhibitory activity will be isolated and characterized. The isolated inhibitory factors will also be utilized in studies designed to elucidate the mechanism of action of this inhibition towards HIV. The elucidation of the molecular structure and mechanism of action of such a factor will not only allow an assessment of the protective effects of saliva against HIV infection, but could lead to strategies for the development of potent anti-HIV agents.